Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Case Reports
. 2025 Mar 10;30(3):oyaf015.
doi: 10.1093/oncolo/oyaf015.

"Incidentally" discovered Von Hippel Lindau disease: an emerging clinical phenotype

Michael N Trinh  1   2 , Lauren Bear  1   3 , Brian V Nahed  4 , Othon Iliopoulos  1   2   5
Affiliations
Case Reports

"Incidentally" discovered Von Hippel Lindau disease: an emerging clinical phenotype

Michael N Trinh et al. Oncologist. .

Abstract

Increasing accessibility to genetic screening for cancer risk can lead to earlier surveillance and prevention, but with this comes the caveat of incidental identification of germline pathogenic gene variants. Here, we report a single institution case series of 6 otherwise healthy individuals with "incidental" Von Hippel Lindau (VHL) disease. These patients were found to have pathogenic germline variants in the VHL gene, after undergoing genetic testing for other purposes (5 for familial breast cancer risk and 1 to determine ancestry) but no VHL disease-associated tumors. The penetrance and expressivity of such incidental variants are not currently known, and therefore, no surveillance guidelines exist. Nevertheless, the association of these variants historically with high disease penetrance compels us to currently recommend active surveillance of their carriers with annual imaging of the brain, spine, and abdomen.

Keywords: Von Hippel Lindau (VHL) disease; germline pathogenic variants; hemangioblastoma; renal cancer.

PubMed Disclaimer

Conflict of interest statement

M.N.T. and L.B. declare no competing interests. B.V.N.: Merck (consultant, one time), Robeaute (consultant), Brianlab (consultant), BK Ultrasound (consultant), REACT Neuro (consultant, co-founder), Zeta (consultant), Leica (consultant). O.I.: Merck (Advisory Board), C4 (consultant), and Calithera, USA (research support).

Figures

Figure 1.
Figure 1.
“Incidental” VHL disease mutations and their positions in the VHL gene and protein structure. Nucleotide and amino acid positions depicted in gene and protein, respectively. Pertinent protein features noted as well including GXEEX acidic repeat sequences.
See this image and copyright information in PMC

References

    1. Shickh S, Clausen M, Mighton C, et al.; Incidental Genomics Study Team. Health outcomes, utility and costs of returning incidental results from genomic sequencing in a Canadian cancer population: protocol for a mixed-methods randomised controlled trial. BMJ Open. 2019;9:e031092. https://doi.org/10.1136/bmjopen-2019-031092 - DOI - PMC - PubMed
    1. Slavin TP, Banks KC, Chudova D, et al.Identification of incidental germline mutations in patients with advanced solid tumors who underwent cell-free circulating tumor DNA sequencing. J Clin Oncol. 2018;36:JCO1800328. https://doi.org/10.1200/JCO.18.00328 - DOI - PMC - PubMed
    1. Ang SO, Chen H, Hirota K, et al.Disruption of oxygen homeostasis underlies congenital Chuvash polycythemia. Nat Genet. 2002;32:614-621. https://doi.org/10.1038/ng1019 - DOI - PubMed
    1. Iliopoulos O. Diseases of hereditary renal cell cancers. Urol Clin North Am. 2023;50:205-215. https://doi.org/10.1016/j.ucl.2023.01.010 - DOI - PubMed
    1. Zhang L, Walsh MF, Jairam S, et al.Fumarate hydratase FH c.1431_1433dupAAA (p.Lys477dup) variant is not associated with cancer including renal cell carcinoma. Hum Mutat. 2020;41:103-109. https://doi.org/10.1002/humu.23900 - DOI - PMC - PubMed

Publication types

Substances